Bioactive Glass Composite Scaffolds Research Articles

Isothermal crystallization behavior of poly-ether-ether-ketone/bioactive glass composites and its correlation with scaffold warpage in laser powder bed fusion process

The preparation of poly-ether-ether-ketone/bioactive glass (PEEK/BG) composite scaffolds using laser powder bed fusion (LPBF) has enormous clinical potential. However, ensuring the desired accuracy and reproducibility of composite scaffolds during the LPBF process remains a significant challenge. Therefore, a thorough understanding of the relationship between the crystallization behaviors and the scaffold warpage during the LPBF process is crucial. To address this challenge, this study systematically investigates the isothermal crystallization kinetics of PEEK/BG composites and their relationship with scaffold warpage. The results reveal that the crystallization rates of pure PEEK and PEEK/BG composites decrease as isothermal crystallization temperature increases. Additionally, BG significantly suppresses the isothermal crystallization kinetics of PEEK, resulting in a 250% increase in the half-crystallization time (t1/2) of PEEK/25 wt% BG at 316 °C relative to pure PEEK. Extrapolating the t1/2 using the Hoffman-Lauritzen model can obtain the optimal powder bed temperature (Tb) for each powder in LPBF. Pure PEEK and PEEK/25 wt% BG Diamond scaffolds are printed at the respective inferred Tb (330 °C and 323 °C) and their warpage degrees are compared to that of the pure PEEK scaffold printed at 323 °C. The results demonstrate that raising Tb from 323 °C to 330 °C and adding 25 wt% BG are both effective methods to reduce the scaffold warpage by slowing down the crystallization kinetics of PEEK, resulting in reductions of 57.8% and 50.6% in warpage degree respectively. Furthermore, the incorporation of BG successfully tackles the challenge of simultaneously preventing warpage and secondary sintering in pure PEEK printing. Overall, this study offers a deep comprehension regarding the relationship between crystallization kinetics and scaffold warpage, which is crucial for achieving the reproducibility with desired accuracy of LPBF-printed biological scaffolds for clinical applications.

Two-dimensional molybdenum disulfide/polymer-coated bioactive glass scaffolds for tissue engineering: Fabrication, structural, mechanical, bioactivity, and radiation interaction properties

Molybdenum disulfide (MoS2)-based nanostructures are widely used in environmental protection and biomedicine owing to their biological, physical, chemical, electrical, and mechanical properties. In this study, polycaprolactone (PCL)- and polylactide-co-glycolide (PLGA)-coated bioactive glass scaffolds containing MoS2 nanoparticles are prepared, and their usability in bone tissue engineering applications is evaluated. Borate bioactive glass scaffolds are fabricated using the replication method and coated with PCL or PLGA solutions (5 wt%) containing MoS2 (0.1, 0.2, 0.5, 1, and 2 wt%) nanoparticles. The structural and mechanical properties of the scaffolds and their bioactivity in simulated body fluids are investigated comprehensively. The ionization–radiation-shielding properties are investigated using Monte Carlo simulations. The results show that the polymer coating layer and presence of MoS2 nanoparticles in the polymer matrix improves the mechanical properties of the scaffolds. The addition of MoS2 nanoparticles to the structure increases the hydroxyapatite-forming ability of bioactive glass-based composites. Additionally, the prepared composite scaffolds exhibit high radiation-shielding ability owing to the presence of MoS2 nanoparticles embedded in the polymer matrix that shields the glass surface. Bioactive glass composite scaffolds containing MoS2 nanoparticles demonstrate promising potential for bone regeneration and radiation-shielding applications.

Preparation and Biocompatibility of Poly Methyl Methacrylate (PMMA)-Mesoporous Bioactive Glass (MBG) Composite Scaffolds.

In recent years, the rising number of bone diseases which affect millions of people worldwide has led to an increased demand for materials with restoring and augmentation properties that can be used in therapies for bone pathologies. In this work, PMMA- MBG composite scaffolds containing ceria (0, 1, 3 mol%) were obtained by the phase separation method. The obtained composite scaffolds were characterized by X-ray diffraction, infrared spectroscopy, and scanning electron microscopy. UV–Vis measurement and EDX analysis confirmed the presence of cerium ions in the composite scaffolds. Evaluation of the in-vitro biocompatibility using MTT assay showed that composite scaffold containing 1 mol% of ceria presented higher viability than control cells (100%) for concentrations ranging between 5 and 50% after 96 h of incubation.

Tungsten disulfide nanoparticle-containing PCL and PLGA-coated bioactive glass composite scaffolds for bone tissue engineering applications

Tungsten disulfide nanoparticle-containing PCL and PLGA-coated bioactive glass composite scaffolds for bone tissue engineering applications

3D printed poly(hydroxybutyrate-co-hydroxyvalerate)—45S5 bioactive glass composite resorbable scaffolds suitable for bone regeneration

3D printing for tissue engineering requires biomaterials with mechanical and biological properties suitable for both tissue regeneration and the printing process. A filament made of poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) combined with 45S5 Bioglass (BG) was used to print 3D scaffolds by fused deposition modeling (FDM). Chemical treatment of BG particles with chlorotrimethylsilane (CTMS) improved the ductility of the extruded filaments and allowed excellent printability. Controlling the printing parameter infill density (I%), from 20 to 90%, scaffolds were obtained with interconnected pores and channel sizes in the 100–800 µm range and exhibiting tensile modulus from 0.25 to 1.36 GPa. PHBV + BG scaffolds and PHBV scaffolds coated with CTMS treated BG particles, as a model of a rough and biologically active coating, showed no cytotoxic effects, and cells preferred the scaffolds containing BG in terms of cell spreading. Mechanical and biological properties of the scaffolds were similar to those of the extracellular matrix (ECM) of trabecular bone.

3D printing of Cu-doped bioactive glass composite scaffolds promotes bone regeneration through activating the HIF-1α and TNF-α pathway of hUVECs.

The increasing insight into the molecular and cellular processes within the angiogenic cascade assists in enhancing the survival and integration of engineered bone constructs. Copper-doped bioactive glass (Cu-BG) is now a potential structural component of the novel scaffolds and implants used in orthopedic and dental repairs. However, it is difficult for BG, especially micro-nano particles, to be printed into scaffolds and still retain its biological activity and ability to biodegrade. Additionally, the mechanisms of the copper-stimulating autocrine and paracrine effects of human umbilical vein endothelial cells (hUVECs) during repair and regeneration of bone are not yet clear. Therefore, in this study, we created monodispersed micro-nano spherical Cu-BG particles with varying copper content through a sol-gel process. Through in vitro tests, we found that Cu-BG enhanced angiogenesis by activating the pro-inflammatory environment and the HIF-1α pathway of hUVECs. Furthermore, 2Cu-BG diluted extracts directly promoted the osteogenic differentiation of mouse bone mesenchymal stem cells (BMSCs) in vitro. Then, a new 3D-printed tyramine-modified gelatin/silk fibroin/copper-doped bioactive glass (Gel/SF/Cu-BG) scaffold for rat bone defects was constructed, and the mechanism of the profound angiogenesis effect regulated by copper was explored in vivo. Finally, we found that hydrogel containing 1 wt% 2Cu-BG effectively regulated the spatiotemporal coupling of vascularization and osteogenesis. Therefore, Cu-BG-containing scaffolds have great potential for a wide range of bone defect repairs.

Polymer-Bioactive Glass Composite Filaments for 3D Scaffold Manufacturing by Fused Deposition Modeling: Fabrication and Characterization.

Critical size bone defects are regularly treated by auto- and allograft transplantation. However, such treatments require to harvest bone from patient donor sites, with often limited tissue availability or risk of donor site morbidity. Not requiring bone donation, three-dimensionally (3D) printed implants and biomaterial-based tissue engineering (TE) strategies promise to be the next generation therapies for bone regeneration. We present here polylactic acid (PLA)-bioactive glass (BG) composite scaffolds manufactured by fused deposition modeling (FDM), involving the fabrication of PLA-BG composite filaments which are used to 3D print controlled open-porous and osteoinductive scaffolds. We demonstrated the printability of PLA-BG filaments as well as the bioactivity and cytocompatibility of PLA-BG scaffolds using pre-osteoblast MC3T3E1 cells. Gene expression analyses indicated the beneficial impact of BG inclusions in FDM scaffolds regarding osteoinduction, as BG inclusions lead to increased osteogenic differentiation of human adipose-derived stem cells in comparison to pristine PLA. Our findings confirm that FDM is a convenient additive manufacturing technology to develop PLA-BG composite scaffolds suitable for bone tissue engineering.

Corrigendum to “Biomimetic characterization reveals enhancement of hydroxyapatite formation by fluid flow in gellan gum and bioactive glass composite scaffolds” [Polym. Test. 76 (2019) 464–472

Corrigendum to “Biomimetic characterization reveals enhancement of hydroxyapatite formation by fluid flow in gellan gum and bioactive glass composite scaffolds” [Polym. Test. 76 (2019) 464–472

Polydopamine-Assisted Anchor of Chitosan onto Porous Composite Scaffolds for Accelerating Bone Regeneration.

Surface function has an importance for the bioactivity of porous polymeric scaffolds. The goal of the present study is to immobilize highly bioactive chitosan (CS) onto the surface of porous composite scaffolds to accelerate bone regeneration. Porous poly(ε-caprolactone) (PCL)/bioactive glass (BG) composite scaffolds with strong anchor of CS were fabricated via mussel-inspired polydopamine (PDA) coating as a bridging layer. In vitro cell culture showed that firm immobilization of CS onto the composite scaffolds significantly enhanced protein adsorption, cell adhesion, and osteogenic differentiation compared to CS-decorated scaffolds via physical adsorption. In vivo assessments demonstrated that covalent immobilization of CS onto the surface of scaffolds obviously promoted cranial bone regeneration in comparison with the counterparts with physical adsorption of CS. The proposed method offers a feasible and effective means to fabricate artificial bioactive scaffolds for bone tissue engineering application.

Biomimetic characterization reveals enhancement of hydroxyapatite formation by fluid flow in gellan gum and bioactive glass composite scaffolds

This study presents production and biomimetic characterization of macroporous composite scaffolds based on gellan gum and nanoparticulate bioactive glass (GG-BAG) under conditions relevant for bone tissue engineering. Formation of hydroxyapatite (HAp) within the scaffolds was investigated in the simulated body fluid (SBF) during 14 days in two biomimetic bioreactors: perfusion bioreactor (1.1 ml/min SBF flowrate) and a bioreactor with coupled dynamic compression and SBF perfusion (5% strain, 0.68 Hz, 1 h on/1 h off, 1.1 ml/min SBF flowrate). HAp formation was evaluated by scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDS) analysis, Fourier transform infrared spectroscopy (FTIR), and X-ray powder diffraction (XRPD). The superficial SBF velocity of 100 μm/s in perfusion bioreactors induced the formation of abundant cauliflower-like HAp crystals throughout the scaffold interior and flake-like crystals on external surfaces resulting in improved mechanical properties as compared to the initial scaffolds. The obtained results indicate potentials of macroporous GG-BAG scaffolds in conjunction with perfusion bioreactors for bone tissue engineering demonstrating high bioactivity suited for cultures of osteogenic cells.

Binary bioactive glass composite scaffolds for bone tissue engineering—Structure and mechanical properties in micro and nano scale. A preliminary study

Composite scaffolds of bioactive glass (SiO2-CaO) and bioresorbable polyesters: poly-l-lactic acid (PLLA) and polycaprolactone (PCL) were produced by polymer coating of porous foams. Their structure and mechanical properties were investigated in micro and nanoscale, by the means of scanning electron microscopy, PeakForce Quantitative Nanomechanical Property Mapping (PF-QNM) atomic force microscopy, micro-computed tomography and contact angle measurements.This is one of the first studies in which the nanomechanical properties (elastic modulus, adhesion) were measured and mapped simultaneously with topography imaging (PF-QNM AFM) for bioactive glass and bioactive glass – polymer coated scaffolds. Our findings show that polymer coated scaffolds had higher average roughness and lower stiffness in comparison to pure bioactive glass scaffolds. Such coating-dependent scaffold properties may promote different cells-scaffold interaction.

In Vitro Degradation of Borosilicate Bioactive Glass and Poly(l-lactide-co-ε-caprolactone) Composite Scaffolds.

Composite scaffolds were obtained by mixing various amounts (10, 30 and 50 weight % [wt %]) of borosilicate bioactive glass and poly(l-lactide-co-ε-caprolactone) (PLCL) copolymer. The composites were foamed using supercritical CO2. An increase in the glass content led to a decrease in the pore size and density. In vitro dissolution/reaction test was performed in simulated body fluid. As a function of immersion time, the solution pH increased due to the glass dissolution. This was further supported by the increasing amount of Ca in the immersing solution with increasing immersion time and glass content. Furthermore, the change in scaffold mass was significantly greater with increasing the glass content in the scaffold. However, only the scaffolds containing 30 and 50 wt % of glasses exhibited significant hydroxyapatite (HA) formation at 72 h of immersion. The compression strength of the samples was also measured. The Young’s modulus was similar for the 10 and 30 wt % glass-containing scaffolds whereas it increased to 90 MPa for the 50 wt % glass containing scaffold. Upon immersion up to 72 h, the Young’s modulus increased and then remained constant for longer immersion times. The scaffold prepared could have great potential for bone and cartilage regeneration.

Manufacturing and Characterization of Highly Porous Bioactive Glass Composite Scaffolds Using Unidirectional Freeze Casting

The aim of this work is the fabrication of bioactive and degradable scaffolds for bone tissue engineering. Freeze casting is used to obtain macropores. Alongside, highly bioactive 45S5 Bioglass, gelatin and chitosan are used as biocompatible binder and stabilizing agent, respectively. By varying the cooling rate between 2 and 4 K min−1 and whether the slurry is allowed to form a gelled network at 7 °C before freeze casting or not, samples with a porosity of 75% are achieved. X‐ray tomography analysis shows smallest pore sizes between 73 and 77 µm and a rather lamellar structure parallel to the freezing direction for the non‐gelled samples, whereas the gelled samples have smallest pores between 96 and 120 µm and show a rather cellular structure. Compression tests reveal compressive strengths from 2 (non‐gelled) to 3 MPa (gelled), while the quasielastic moduli of the gelled samples (44–46 MPa) clearly exceed values of the non‐gelled (20–23 MPa). Thus, it is concluded that the modified pore structure caused by the gelling process markedly improves the mechanical properties of the samples. After seven days in SBF under physiological conditions, a calcium phosphate rich layer is detected on the samples surface, revealing the bioactivity of the scaffolds.

Electrically conductive borate-based bioactive glass scaffolds for bone tissue engineering applications.

In this study, electrically conductive, borate-based, porous 13-93B3 bioactive glass composite scaffolds were prepared using a polymer foam replication technique. For this purpose, a slurry containing 40 vol% glass particles and 0-10 wt% graphene nanoplatelets was prepared by dispersing the particles in ethanol in the presence of ethyl cellulose. Composite scaffolds were subjected to a controlled heat treatment, in air atmosphere, to decompose the foam and sinter the glass particles into a dense network. It was found that the applied heat treatment did not influence the structure of graphene in the glass network. Graphene additions did not negatively affect the mechanical properties and enhanced the electrical conductivity of the glass scaffolds. In X-ray diffraction analysis, the crystalline peak corresponding to hydroxyapatite was observed in all the samples suggesting that all of the samples were bioactive after 30 days of immersion in simulated body fluid. However, Fourier transform infrared spectroscopy analysis and scanning electron microscope observations revealed that hydroxyapatite formation rate decreased with increasing graphene concentration especially for samples treated in simulated body fluid for shorter times. Based on the cytotoxicity assay findings, the MC3T3-E1 cell growth was significantly inhibited by the scaffolds containing higher amount of graphene compared to bare glass scaffolds. Best performance was obtained for 5 wt% graphene which yielded an enhancement of electrical conductivity with moderate cellular response and invitro hydroxyapatite forming ability. The study revealed that the electrically conductive 13-93B3 graphene scaffolds are promising candidates for bone tissue engineering applications.

Reinforcement with reduced graphene oxide of bioactive glass scaffolds fabricated by robocasting

45S5 bioactive glass composite scaffolds reinforced with reduced graphene oxide (rGO) were fabricated for the first time by robocasting (direct-writing) technique. Composite scaffolds with 0–3vol.% content of rGO platelets were printed, and then consolidated by pressureless sintering at 550 or 1000°C in Ar atmosphere. It was found that the addition of rGO platelets up to 1.5vol.% content enhanced the mechanical performance of the 45S5 bioactive glass scaffolds in terms of strength and toughness. Best performance was obtained for 1vol.% rGO, which yielded an enhancement of the fracture toughness of ∼850 and 380% for sintering temperatures of 550 and 1000°C, respectively, while the compressive strength increased by ∼290 and 75%. rGO addition thus emerges as a promising approach for the fabrication of novel bioglass scaffolds with improved mechanical performance without deterioration of their bioactivity, which may then find use in load-bearing bone tissue engineering applications.

Fabrication and characterization of poly(ɛ-caprolactone) coated silicate and borate-based bioactive glass composite scaffolds

In this study, silicate 13-93 and borate based 13-93B3 bioactive glass scaffolds with high porosity and interconnected pore structure (pore size 100–500 µm) were prepared by foam replication method. In order to improve the mechanical properties, the scaffolds were coated and infiltrated with a poly(ɛ-caprolactone) (PCL) solution at different concentrations (5, 10, and 20 wt%). Results revealed that the mechanical properties of the scaffolds were significantly improved by the PCL coating. The addition of 10% PCL coating led to approximately 10-fold increase of compressive strength in comparison with noncoated scaffolds. The bioactivity of scaffolds upon immersion in simulated body fluid was maintained in the PCL-coated scaffolds at all concentrations; however, a decrease in the formation rate and amount of crystalline hydroxyapatite was observed as the PCL concentration was increased in the coating layer. Degradation rate of the borate-based bioactive glass scaffolds was tailored by the PCL coating. It is concluded that the fabricated bioactive composite scaffolds represent promising candidates for bone tissue engineering applications.

Fabrication and characterization of zein–bioactive glass scaffolds

Plant proteins show advantages over animal-based proteins for biomaterial applications attributable to their ease of availability and suitable biodegradability. In this study, composite foams based on zein and 45S5 bioactive glass (BG) particles were produced through salt leaching for potential applications in bone tissue engineering (BTE) applications. Different characterization techniques were used including scanning electron microscopy for morphological and microstructural analysis, ATR-FTIR spectroscopy and X-ray diffraction for composition characterization and mechanical tests. Zein–BG composite scaffolds demonstrate enhanced bioactivity with a compressive modulus and strength around 5·7 MPa and 1·9 MPa, respectively. Zein–BG composite scaffolds constitute a new bioactive material with potential applications in BTE.

In vitro degradation and bioactivity of poly(propylene fumarate)/bioactive glass sintered microsphere scaffolds for bone tissue engineering

Abstract We developed degradable poly(propylene fumarate)/bioactive glass (PPF/BG) composite scaffolds based on a sintered microsphere technique and investigated the effects of BG content on the characteristics of these composite scaffolds. Immersion in a simulated body fluid (SBF) was used to evaluate the surface reactivity of composite scaffolds. The surface of composite scaffolds was covered with hydroxycarbonate apatite layer after 7 days of immersion. Ion concentration analyses revealed a decrease in P concentration and an increase in Si, Ca, and Sr concentrations in SBF immersed with composite scaffolds during the 3-week period. The Ca and P uptake rates decreased after 4 days of incubation. This coincided with the decrease of the Si release rate. These data lend support to the suggestion that the Si released from the BG content of scaffolds present in the polymer matrix was involved in the formation of the Ca-P layer. The evaluation of the in vitro degradation of composite microspheres revealed that the weight of scaffolds remained relatively constant during the first 3 weeks and then started to decrease slowly, losing 10.5% of their initial mass by week 12. Our results support the concept that these new bioactive, degradable composite scaffolds may be used for bone tissue engineering applications.

Three dimensionally printed mesoporous bioactive glass and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) composite scaffolds for bone regeneration.

Development of bioactive scaffolds with controllable architecture and high osteogenic capability for bone tissue engineering is hotly pursued. In this study, three-dimensional (3D) mesoporous bioactive glass (MBG) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds with well-defined pore structures and high compressive strength (∼5-12 MPa) were synthesized by a 3D printing technique. Compared to reported polymer-bonded MBG scaffolds, the incorporation of the biocompatible PHBHHx polymer as a particle binder enhanced their bioactive and osteogenic properties, including fast apatite-forming ability, and promoted human bone marrow-derived mesenchymal stem cell (hBMSC) adhesion, proliferation, alkaline phosphatase (ALP) activity and bone-related gene expression. Furthermore, MBG/PHBHHx composite scaffolds were explored to repair critical-size rat calvarial defects. The results showed that MBG/PHBHHx composite scaffolds exhibited a controlled degradation rate and more significant potential to stabilize the pH environment with increasing PHBHHx ratio. At 8 weeks post-implantation, MBG/PHBHHx scaffolds were demonstrated to stimulate bone regeneration in the calvarial defects and have largely repaired them through analysis of micro-CT, sequential fluorescent labeling and histology. These results lay a potential framework for future study by using modified MBG/PHBHHx-based functional scaffolds to improve the osteogenic activity and bone defect restoration.

Preparation and characterization of PHBV microsphere/45S5 bioactive glass composite scaffolds with vancomycin releasing function

PHBV microsphere/45S5 bioactive glass (BG) composite scaffolds with drug release function were developed for bone tissue engineering. BG-based glass-ceramic scaffolds with high porosity (94%) and interconnected pore structure prepared by foam replication method were coated with PHBV microspheres (nominal diameter=3.5μm) produced by water-in-oil-in-water double emulsion solvent evaporation method. A homogeneous microsphere coating throughout the porous structure of scaffolds was obtained by a simple dip coating method, using the slurry of PHBV microspheres in hexane. Compressive strength tests showed that the microsphere coating slightly improved the mechanical properties of the scaffolds. It was confirmed that the microsphere coating did not inhibit the bioactivity of the scaffolds in SBF. Hydroxyapatite crystals homogeneously grew not only on the struts of the scaffolds but also on the surface of microspheres within 7days of immersion in SBF. Vancomycin was successfully encapsulated into the PHBV microspheres. The encapsulated vancomycin was released with a dual release profile involving a relatively low initial burst release (21%) and a sustained release (1month), which is favorable compared to the high initial burst release (77%) and short release period (4days) measured on uncoated scaffolds. The developed bioactive composite scaffold with drug delivery function has thus the potential to be used advantageously in bone tissue engineering.